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Molecular motions in drug design: the coming age of the metadynamics method

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Abstract

Metadynamics is emerging as a useful free energy method in physics, chemistry and biology. Recently, it has been applied also to investigate ligand binding to biomolecules of pharmacological interest. Here, after introducing the basic idea of the method, we review applications to challenging targets for pharmaceutical intervention. We show that this methodology, especially when combined with a variety of other computational approaches such as molecular docking and/or molecular dynamics simulation, may be useful to predict structure and energetics of ligand/target complexes even when the targets lack a deep binding cavity, such as DNA and proteins undergoing fibrillation in neurodegenerative diseases. Furthermore, the method allows investigating the routes of molecular recognition and the associated binding energy profiles, providing a molecular interpretation to experimental data.

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Acknowledgments

A. V. Vargiu acknowledges financial support from “Regione Autonoma della Sardegna” through a Research Fellow on fundings “PO Sardegna FSE 2007-2013, L.R.7/2007 Promozione della ricerca scientifica e dell’innovazione tecnologica in Sardegna”. X. Biarnés acknowledges financial support from “Generalitat de Catalunya” through a “Beatriu de Pinos” research fellow.

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Authors and Affiliations

  1. International School for Advanced Studies, Trieste, Italy

    Xevi Biarnés, Salvatore Bongarzone & Paolo Carloni

  2. Istituto Officina dei Materiali del CNR—Unità SLACS, Cagliari, Italy

    Attilio Vittorio Vargiu

  3. Department of Physics, University of Cagliari, Cagliari, Italy

    Attilio Vittorio Vargiu & Paolo Ruggerone

  4. German Research School, Julich Research Center, Julich and RWTH, Aachen, Germany

    Paolo Carloni

Authors
  1. Xevi Biarnés
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  2. Salvatore Bongarzone
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  3. Attilio Vittorio Vargiu
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  4. Paolo Carloni
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  5. Paolo Ruggerone
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Corresponding author

Correspondence to Paolo Ruggerone.

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The authors Xevi Biarnés, Salvatore Bongarzone, Attilio Vittorio Vargiu contributed equally to this work.

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Biarnés, X., Bongarzone, S., Vargiu, A.V. et al. Molecular motions in drug design: the coming age of the metadynamics method. J Comput Aided Mol Des 25, 395–402 (2011). https://doi.org/10.1007/s10822-011-9415-3

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  • DOI: https://doi.org/10.1007/s10822-011-9415-3

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